Histamine H1 antagonists are among the most frequently used drugs in contemporary society and are abused in combination with opioids by certain drug-dependent populations. Our previous work has shown that prototypical H1 antagonists have striking effects on schedule-controlled behavior that can be attenuated by the dopamine antagonist haloperidol. One major focus of the proposed research is to evaluate further the role of dopamine- related actions in the behavioral effects of H1 antagonists by: 1) comparing the effects of H1 antagonists with those of selective D1 and D2 agonists and 2) studying how the behavioral effects of H1 antagonists are altered by selective D1 and D2 antagonists. We previously have found that selected H1 antagonists can maintain persistent drug-taking behavior in squirrel monkeys. A second focus of this project is to extend these findings by: 1) studying the development of self-administration in drug-naive subjects, 2) evaluating the effects of self-administered H1 antagonists on other ongoing behavior, and 3) investigating how the reinforcing effects of H1 antagonists are modified by dopamine D1 and D2 antagonists. Our ongoing research indicates that H1 antagonists can potentiate the behavioral effects of cocaine and caffeine. A third focus of the proposed research is to extend these studies by systematically determining how H1 antagonists modify the reinforcing and other behavioral effects of cocaine, caffeine, and nicotine. The final objective of the proposed research is to continue our evaluation of the behavioral effects of opioids alone and in combination with histamine H1 antagonists. We will assess interactions between these drug classes by determining how H1 antagonists modify the reinforcing and other behavioral effects of pentazocine and other opioids. Overall, the proposed research will provide needed information about pharmacological and environmental factors mediating the behavioral effects of histamine H1 antagonists alone and in combination with other commonly used drugs.